BACKGROUND: Mitral valve prolapse (MVP) is a common disorder associated with mitral regurgitation, endocarditis, heart failure, and sudden death. To date, 2 MVP loci have been described, but the defective genes have yet to be discovered. In the present study, we analyzed a large family segregating MVP, and identified a new locus, MMVP3. This study and others have enabled us to explore mitral valve morphological variations of currently uncertain clinical significance. METHODS AND RESULTS: Echocardiograms and blood samples were obtained from 43 individuals who were classified by the extent and pattern of displacement. Genotypic analyses were performed with polymorphic microsatellite markers. Evidence of linkage was obtained on chromosome 13q31.3-q32.1, with a peak nonparametric linkage score of 18.41 (P<0.0007). Multipoint parametric analysis gave a logarithm of odds score of 3.17 at marker D13S132. Of the 6 related individuals with mitral valve morphologies not meeting diagnostic criteria but resembling fully developed forms, 5 carried all or part of the haplotype linked to MVP. CONCLUSIONS: The mapping of a new MVP locus to chromosome 13 confirms the observed genetic heterogeneity and represents an important step toward gene identification. Furthermore, the genetic analysis provides clinical lessons with regard to previously nondiagnostic morphologies. In the familial context, these may represent early expression in gene carriers. Early recognition of gene carriers could potentially enhance the clinical evaluation of patients at risk of full expression, with the ultimate aim of developing interventions to reduce progression.
BACKGROUND:Mitral valve prolapse (MVP) is a common disorder associated with mitral regurgitation, endocarditis, heart failure, and sudden death. To date, 2 MVP loci have been described, but the defective genes have yet to be discovered. In the present study, we analyzed a large family segregating MVP, and identified a new locus, MMVP3. This study and others have enabled us to explore mitral valve morphological variations of currently uncertain clinical significance. METHODS AND RESULTS: Echocardiograms and blood samples were obtained from 43 individuals who were classified by the extent and pattern of displacement. Genotypic analyses were performed with polymorphic microsatellite markers. Evidence of linkage was obtained on chromosome 13q31.3-q32.1, with a peak nonparametric linkage score of 18.41 (P<0.0007). Multipoint parametric analysis gave a logarithm of odds score of 3.17 at marker D13S132. Of the 6 related individuals with mitral valve morphologies not meeting diagnostic criteria but resembling fully developed forms, 5 carried all or part of the haplotype linked to MVP. CONCLUSIONS: The mapping of a new MVP locus to chromosome 13 confirms the observed genetic heterogeneity and represents an important step toward gene identification. Furthermore, the genetic analysis provides clinical lessons with regard to previously nondiagnostic morphologies. In the familial context, these may represent early expression in gene carriers. Early recognition of gene carriers could potentially enhance the clinical evaluation of patients at risk of full expression, with the ultimate aim of developing interventions to reduce progression.
Authors: Francesca N Delling; Jian Rong; Martin G Larson; Birgitta Lehman; Ewa Osypiuk; Plamen Stantchev; Susan A Slaugenhaupt; Emelia J Benjamin; Robert A Levine; Ramachandran S Vasan Journal: Circulation Date: 2014-10-31 Impact factor: 29.690
Authors: Robert A Levine; Albert A Hagége; Daniel P Judge; Muralidhar Padala; Jacob P Dal-Bianco; Elena Aikawa; Jonathan Beaudoin; Joyce Bischoff; Nabila Bouatia-Naji; Patrick Bruneval; Jonathan T Butcher; Alain Carpentier; Miguel Chaput; Adrian H Chester; Catherine Clusel; Francesca N Delling; Harry C Dietz; Christian Dina; Ronen Durst; Leticia Fernandez-Friera; Mark D Handschumacher; Morten O Jensen; Xavier P Jeunemaitre; Hervé Le Marec; Thierry Le Tourneau; Roger R Markwald; Jean Mérot; Emmanuel Messas; David P Milan; Tui Neri; Russell A Norris; David Peal; Maelle Perrocheau; Vincent Probst; Michael Pucéat; Nadia Rosenthal; Jorge Solis; Jean-Jacques Schott; Ehud Schwammenthal; Susan A Slaugenhaupt; Jae-Kwan Song; Magdi H Yacoub Journal: Nat Rev Cardiol Date: 2015-10-20 Impact factor: 32.419
Authors: Francesca N Delling; Philimon Gona; Martin G Larson; Birgitta Lehman; Warren J Manning; Robert A Levine; Emelia J Benjamin; Ramachandran S Vasan Journal: J Am Soc Echocardiogr Date: 2013-10-24 Impact factor: 5.251
Authors: Katelynn A Toomer; Mengyao Yu; Diana Fulmer; Lilong Guo; Kelsey S Moore; Reece Moore; Ka'la D Drayton; Janiece Glover; Neal Peterson; Sandra Ramos-Ortiz; Alex Drohan; Breiona J Catching; Rebecca Stairley; Andy Wessels; Joshua H Lipschutz; Francesca N Delling; Xavier Jeunemaitre; Christian Dina; Ryan L Collins; Harrison Brand; Michael E Talkowski; Federica Del Monte; Rupak Mukherjee; Alexander Awgulewitsch; Simon Body; Gary Hardiman; E Starr Hazard; Willian A da Silveira; Baolin Wang; Maire Leyne; Ronen Durst; Roger R Markwald; Solena Le Scouarnec; Albert Hagege; Thierry Le Tourneau; Peter Kohl; Eva A Rog-Zielinska; Patrick T Ellinor; Robert A Levine; David J Milan; Jean-Jacques Schott; Nabila Bouatia-Naji; Susan A Slaugenhaupt; Russell A Norris Journal: Sci Transl Med Date: 2019-05-22 Impact factor: 17.956